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The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive fu...

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Autores principales: Skvarc, David R., Dean, Olivia M., Byrne, Linda K., Gray, Laura J., Ives, Kathryn, Lane, Stephen E., Lewis, Matthew, Osborne, Cameron, Page, Richard, Stupart, Douglas, Turner, Alyna, Berk, Michael, Marriott, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977889/
https://www.ncbi.nlm.nih.gov/pubmed/27502769
http://dx.doi.org/10.1186/s13063-016-1529-4
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author Skvarc, David R.
Dean, Olivia M.
Byrne, Linda K.
Gray, Laura J.
Ives, Kathryn
Lane, Stephen E.
Lewis, Matthew
Osborne, Cameron
Page, Richard
Stupart, Douglas
Turner, Alyna
Berk, Michael
Marriott, Andrew J.
author_facet Skvarc, David R.
Dean, Olivia M.
Byrne, Linda K.
Gray, Laura J.
Ives, Kathryn
Lane, Stephen E.
Lewis, Matthew
Osborne, Cameron
Page, Richard
Stupart, Douglas
Turner, Alyna
Berk, Michael
Marriott, Andrew J.
author_sort Skvarc, David R.
collection PubMed
description BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting. METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress. DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial. TRIAL REGISTRATION: The PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640; registered on 15 April 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1529-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-49778892016-08-10 The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial Skvarc, David R. Dean, Olivia M. Byrne, Linda K. Gray, Laura J. Ives, Kathryn Lane, Stephen E. Lewis, Matthew Osborne, Cameron Page, Richard Stupart, Douglas Turner, Alyna Berk, Michael Marriott, Andrew J. Trials Study Protocol BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting. METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress. DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial. TRIAL REGISTRATION: The PANACEA trial has been registered with the Therapeutic Goods Administration, and the Australian New Zealand Clinical Trials Registry: ACTRN12614000411640; registered on 15 April 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1529-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-09 /pmc/articles/PMC4977889/ /pubmed/27502769 http://dx.doi.org/10.1186/s13063-016-1529-4 Text en © Skvarc et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Skvarc, David R.
Dean, Olivia M.
Byrne, Linda K.
Gray, Laura J.
Ives, Kathryn
Lane, Stephen E.
Lewis, Matthew
Osborne, Cameron
Page, Richard
Stupart, Douglas
Turner, Alyna
Berk, Michael
Marriott, Andrew J.
The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title_full The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title_fullStr The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title_full_unstemmed The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title_short The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial
title_sort post-anaesthesia n-acetylcysteine cognitive evaluation (panacea) trial: study protocol for a randomised controlled trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977889/
https://www.ncbi.nlm.nih.gov/pubmed/27502769
http://dx.doi.org/10.1186/s13063-016-1529-4
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